cIII

Gene Description

Small oligomeric amphipathic alpha-helical protease inhibitor (54 amino acids) of Escherichia phage lambda that promotes the establishment of lysogeny by inhibiting the host ATP-dependent membrane metalloprotease FtsH (HflB). Expressed during early infection from the leftward promoter PL, CIII binds directly to FtsH and acts as a competitive inhibitor that prevents FtsH from binding and degrading the unstable phage transcriptional activator CII (as well as the host heat-shock sigma factor sigma32). By extending the half-life of CII, CIII enables coordinate activation of the PRE, PI, and PaQ promoters required for prophage integration and repression of lytic development.

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0019042 viral latency	IEA GO_REF:0000043	ACCEPT	Summary: Electronic annotation from UniProtKB keyword mapping for viral latency. Reason: CIII promotes the establishment of viral latency (lysogeny) by competitively inhibiting host FtsH-mediated proteolysis of the lysogenic activator CII. Supporting Evidence: PMID:18721134 The CIII protein of bacteriophage lambda exhibits antiproteolytic activity against the ubiquitous metalloprotease HflB (FtsH) of Escherichia coli, thereby stabilizing the lambdaCII protein and promoting lysogenic development of the phage. PMID:17426811 Here we show that the protease inhibitor CIII is present as oligomeric amphipathic alpha helical structures and functions as a competitive inhibitor of FtsH by preventing binding of the CII substrate.
GO:0004866 endopeptidase inhibitor activity	IDA PMID:17426811 Phage lambda CIII: a protease inhibitor regulating the lysis...	NEW	Summary: Direct experimental demonstration that CIII acts as a competitive protease inhibitor of host FtsH (HflB). Reason: Biochemical and genetic assays demonstrate that lambda CIII directly binds and competitively inhibits the host metalloprotease FtsH (HflB), preventing proteolysis of CII and sigma32. Supporting Evidence: PMID:17426811 Here we show that the protease inhibitor CIII is present as oligomeric amphipathic alpha helical structures and functions as a competitive inhibitor of FtsH by preventing binding of the CII substrate.

Core Functions

Competitively inhibits the host inner-membrane metalloprotease FtsH (HflB) by direct binding to prevent proteolytic degradation of the phage transcriptional activator CII, thereby promoting the establishment of viral latency.

Molecular Function:

endopeptidase inhibitor activity

Directly Involved In:

viral latency

Supporting Evidence:

PMID:17426811
Here we show that the protease inhibitor CIII is present as oligomeric amphipathic alpha helical structures and functions as a competitive inhibitor of FtsH by preventing binding of the CII substrate.
PMID:18721134
The CIII protein of bacteriophage lambda exhibits antiproteolytic activity against the ubiquitous metalloprotease HflB (FtsH) of Escherichia coli, thereby stabilizing the lambdaCII protein and promoting lysogenic development of the phage.

References

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Suggested Experiments

Experiment: Cryo-EM structural determination of the membrane-reconstituted Escherichia coli FtsH hexamer bound to oligomeric lambda CIII peptides in the presence of ATPgammaS.

Hypothesis: CIII oligomers bind across multiple FtsH protomers near the substrate entry pore, sterically blocking C-terminal degron engagement while resisting single-chain translocation into the proteolytic chamber.

Gene Description

Existing Annotations Review

Core Functions

Competitively inhibits the host inner-membrane metalloprotease FtsH (HflB) by direct binding to prevent proteolytic degradation of the phage transcriptional activator CII, thereby promoting the establishment of viral latency.

References

Suggested Questions for Experts

Suggested Experiments

📚 Additional Documentation

Notes

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